The Aim is to further develop and commercialize a new instrument that uniquely senses small specific intermolecular interactions. The Bioprobe Force Microscope (BFM) utilizes functionalized biospecific tips and modified atomic force microscopy controller functions. Phase I found we could measure binding forces between beta-adrenoreceptors (BAR), a biomedically important receptor, and an antagonist drug. The Specific Aims of Phase II are to measure in control and test periods specific binding forces between: (1) membrane proteins, specifically receptors and channels and their ligands, and (2) nonmembrane globular proteins and interacting molecules. Areas have been chosen because of their scientific and clinical potential. Area Resource Persons are experts in these Areas of membrane and globular proteins. They have identified the potential usefulness of the BFM in their area of science and have contributed to the protocols. Phase II focuses on, but is not limited to: (1) membrane proteins including BARs, insulin receptors, oxytocin receptors and sodium channels, and (2) globular proteins including lipoproteins, prions, and proteins that interact with crystals to prevent kidney stones. The principle behind the single product of Phase I has been extended to biomedically important proteins which, in turn, should develop into commercial products and services. The advancements in Phase II will be generalizable to a universe of applications in which it is important to have information on the interaction between molecules. Since Phase I, patent protection has been obtained for the functionalized tips, making the products more attractive commercially. PROPOSED COMMERCIAL APPLICATION The distinctive advantages of AFM technology in the biological force measurement are its extended force range, the ability to make scanning tips biospecific, high spatial resolution, and nanometer control of x, y and z movement. The ability of the biospecific tips, called bioprobes, is to measure the interaction.